Abnormal cell proliferation is a hallmark of various pathological conditions. In particular, uncontrolled cell growth is associated with diseases such as fibrosis (e.g., hepatic fibrosis), and various other diseases and conditions associated with abnormal cell proliferation, including cancer.
For example, chronic hepatitis is characterized as an inflammatory liver disease continuing for at least six months without improvement. Chronic hepatitis C represents one form of chronic hepatitis. Left unchecked, chronic hepatitis C can progress to cirrhosis and extensive necrosis of the liver. Although chronic hepatitis C is often associated with deposition of collagen type I leading to hepatic fibrosis, the mechanisms of fibrogenesis remain unknown. Indeed, there is no established treatment for hepatic fibrogenesis related to the over-production of collagen type I (See e.g., Maher and McGuire, J. Clin. Invest. 86:1641-48 (1990); Chojkier Pathogenesis of hepatic fibrosis. In Extracellular Matrix, Marcel Dekker Inc., New York, N.Y., pp. 541-57 (1993)). However, it is known that ribosomal protein S-6 kinases (RSKs) are critical for survival of cells such as the hepatic stellate cells that overproduce the fibrous tissue that results in cirrhosis. Nonetheless, despite the tremendous research effort and funding dedicated to fibrotic diseases (e.g., hepatic fibrosis), there remains a need in the art for compositions and methods that are effective in suppressing the activation and/or proliferation of abnormal cells, including cancer cells.